Aronoff G R, Bergstrom R F, Bopp R J, Sloan R S, Callaghan J T
Department of Medicine, University of Louisville, KY 40292.
Clin Pharmacol Ther. 1988 Jun;43(6):688-95. doi: 10.1038/clpt.1988.97.
To test the hypothesis that renal insufficiency alters nizatidine disposition, we determined the pharmacokinetics of nizatidine and its major metabolite after a single oral dose in normal volunteers and patients with various degrees of renal dysfunction, after a single intravenous dose in normal volunteers and patients with severe renal failure and during hemodialysis. After intravenous administration the elimination half-life increased from 1.5 +/- 0.2 hours in normal volunteers to 6.9 +/- 3.3 hours in patients with renal failure. The plasma clearance decreased from 0.59 +/- 0.07 L/kg/hr in normal volunteers to 0.14 +/- 0.02 L/kg/hr in patients with renal failure. Nizatidine bioavailability was nearly 100% in normal volunteers but decreased to 75% in patients with renal failure. The volume of distribution was 1.3 +/- 0.1 L/kg in normal volunteers and was not different in patients with renal failure. Nizatidine protein binding was about 30% in normal and uremic plasma. The drug was not substantially removed by hemodialysis. Patients with creatinine clearances less than 50 ml/min/1.73 m2 should receive 150 mg nizatidine once each evening. Patients with creatinine clearances less than 20 ml/min/1.73 m2 should receive 150 mg nizatidine every other night.
为验证肾功能不全是否会改变尼扎替丁的处置过程这一假设，我们测定了正常志愿者和不同程度肾功能不全患者单次口服给药后、正常志愿者和严重肾衰竭患者单次静脉给药后以及血液透析期间尼扎替丁及其主要代谢产物的药代动力学。静脉给药后，消除半衰期从正常志愿者的1.5±0.2小时增加至肾衰竭患者的6.9±3.3小时。血浆清除率从正常志愿者的0.59±0.07 L/kg/小时降至肾衰竭患者的0.14±0.02 L/kg/小时。尼扎替丁在正常志愿者中的生物利用度接近100%，但在肾衰竭患者中降至75%。正常志愿者的分布容积为1.3±0.1 L/kg，肾衰竭患者的分布容积无差异。尼扎替丁在正常血浆和尿毒症血浆中的蛋白结合率约为30%。血液透析不能显著清除该药物。肌酐清除率低于50 ml/min/1.73 m2的患者应每晚服用150 mg尼扎替丁。肌酐清除率低于20 ml/min/1.73 m2的患者应每隔一晚服用150 mg尼扎替丁。
